February 18, 2011 — A low score on Apgar, a test that evaluates physical signs during the first 5 minutes of a newborn's life, may be linked to an increased risk for attention-deficit/hyperactivity disorder (ADHD), new research suggests.
In a population study of all children born between 1988 and 2001 in Denmark, investigators found that those with the lowest scores had a 75% higher risk of developing ADHD in childhood than those with the highest scores.
Dr. Jiong Li
"The finding confirms the general practice of having this measure as a routine part of pediatric history taking," lead study author Jiong Li, MD, PhD, associate professor in the Department of Epidemiology in the School of Public Health at the University of Aarhus, Denmark, told Medscape Medical News.
"However, we do not find that the predictive value is so good that we should routinely inform parents with a child with a low Apgar score about the higher risk of ADHD. Still, for those with a family disposition to ADHD, it may be relevant to do so," added Dr. Li.
The study was published online January 18 in the Journal of Pediatrics.
Etiology Not Established
The Apgar score, which was developed half a century ago, is used in countries all over the world and assigned to almost every child born in a hospital, report the investigators. The best scores are a 9 or 10, whereas a score of 7 or above is considered "normal."
Dr. Li said that "quite frequently" many infants are born with a low Apgar score, which might imply adverse health outcomes in future life.
"Several studies have shown that low scores can be linked to neurologic diseases, such as cerebral palsy, epilepsy, mental retardation, and intelligence quotients," write the researchers.
However, a clear link between a low score and ADHD risk has not been shown before, they add, noting that almost 5% of children worldwide have the disorder.
"ADHD has a fetal origin but the etiology is not clear. So it is important to estimate the relative importance of a low Apgar score in the development of ADHD in order for clinicians to decide whether they should do something," explained Dr. Li.
"Our previous research indicated that prenatal stress might play a role in causing low Apgar scores and also ADHD development. I thus wanted to evaluate the association between the two," he said.
The investigators assessed data on 980,902 children. All were monitored from 3 years of age until either a first International Classification of Diseases diagnosis of hyperkinetic disorder, a first medication for ADHD, migration, or death until the end of 2006.
Inverse Association
Results showed that 8234 of the final study population of 903,515 had ADHD (82% male).
"Male ***, small for gestational age, younger mothers, lower socioeconomic status, and parental history of psychiatric illness were correlated with higher incidence rates of ADHD," report the researchers.
In addition, the Apgar scores were found to be inversely associated with risk for ADHD (adjusted hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.88 – 0.96, P < .001).
The risk for ADHD was significantly higher in the children with Apgar scores of 1 to 4 (HR, 1.75; 95% CI, 1.15 – 2.11) and with scores of 5 to 6 (HR, 1.63; 95% CI, 1.25 – 2.11) compared to the children with the highest scores of 9 or 10.
"Our findings, taken together with previous observations, indicate that the Apgar score may be a valuable predictor of subtle neurodevelopmental disabilities such as ADHD," write the study authors.
Dr. Li said the investigators are now planning a bigger population-based study that will focus on other risk factors for ADHD and assess the relative importance of a low Apgar score in the causal pathway to ADHD.
"In the meantime, we will implement a study that has biological markers for prenatal stress for a selection of study participants to investigate the underlying biological mechanisms for the connection," he added.
'Rudimentary but Possible'
Dr. Mani Pavuluri
"Overall, I think this is a good study, but large studies such as this that collapse 1 finding as so prominent is always worrying. It could lend itself to misinterpretation given that there are so many other features that are potentially influencing the outcome in regards to ADHD," Mani Pavuluri, MD, PhD, Berger-Colbeth Endowed Chair in Child Psychiatry and director of the Pediatric Brain Research and Intervention Center at the University of Illinois at Chicago, told Medscape Medical News.
"ADHD has multiple causes and there can be many, many reasons for a low Apgar score. So a low score does not necessarily mean it will result in ADHD," added Dr. Pavuluri, who was not involved with this study.
She noted that reasons for the low score can include an infant being born very prematurely with intracerebral hemorrhage, by asphyxia from "a cord around the neck," or by poor blood supply in utero.
"Any insult prenatally could possibly result in neurologic problems. And for ADHD, one of the causes is from neurological difficulties early on that could lead to some cognitive impairment.
"So, while saying that lower Agpar score leads to ADHD is being slightly rudimentary, it is also potentially possible," she said.
Dr. Pavuluri, who is also a spokesperson for the American Academy of Child and Adolescent Psychiatry, said she would tell mothers of children with lower Apgar scores to pay close attention to developmental milestones.
"Also, look for any signs of increased motor activity, so much so that they are not able to control the child — especially in the early years of development. Also, when children go to kindergarten, monitor whether they are able to cope with the structured environment.
"Overall, I'd say that these study findings are very important but not an end-all," she concluded.
The study was funded by grants from the Danish Medical Research Council, the Nordic Cancer Union, and the European Research Council. The study authors and Dr. Pavuluri have disclosed no relevant financial relationships.
J Pediatr. Published online January 18, 2011.

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